We are applying quantum mechanics without semiempirical input to the study of the electronic structure of large molecules and the interaction of these molecules with themselves (intermolecular forces) and with external electromagnetic fields (transition probabilities). We seek to work from first principles, generating an effective Hamiltonian for the subset of electron states explicitly considered by performing a canonical (unitary) transformation upon the given Coulombic Hamiltonian. Indeed, one of our goals is to justify on the basis of this transformation of the semiempirical parameters usually adopted in molecular calculations. We have derived formal expressions based on cluster expansion techniques to write down explicitly the one-two- and many-body terms appearing in the canonically transformed Hamiltonian. Presently, we are developing numerical techniques and computer codes to implement this formalism. A general oscillator strength (f value) program for Gaussian orbitals has recently been completed. The transformation will be applied to the sigma-pi separability problem in planar molecules. Calculations on the peptide linkage, a series of planar hydrocarbons, and ultimately the pi-electron structure of DNA bases are envisioned.